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Causality and PsychopathologyFinding the Determinants of Disorders and their Cures$
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Patrick Shrout, Katherine Keyes, and Katherine Ornstein

Print publication date: 2011

Print ISBN-13: 9780199754649

Published to Oxford Scholarship Online: November 2020

DOI: 10.1093/oso/9780199754649.001.0001

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Obtaining Robust Causal Evidence from Observational Studies: Can Genetic Epidemiology Help?

Obtaining Robust Causal Evidence from Observational Studies: Can Genetic Epidemiology Help?

9 Obtaining Robust Causal Evidence from Observational Studies: Can Genetic Epidemiology Help?
Causality and Psychopathology

George Davey Smith

Oxford University Press

Observational epidemiological studies have clearly made important contributions to understanding the determinants of population health. However, there have been high-profile problems with this approach, highlighted by apparently contradictory findings emerging from observational studies and from randomized controlled trials (RCTs) of the same issue. These situations, of which the best known probably relates to the use of hormone-replacement therapy (HRT) in coronary heart disease (CHD) prevention, have been discussed elsewhere (Davey Smith & Ebrahim, 2002) . The HRT controversy is covered elsewhere in this volume (see Chapter 5). Here, I will discuss two examples. First, consider the use of vitamin E supplements and CHD risk. Several observational studies have suggested that the use of vitamin E supplements is associated with a reduced risk of CHD, two of the most influential being the Health Professionals Follow-Up Study (Rimm et al., 1993) and the Nurses’ Health Study (Stampfer et al., 1993), both published in the New England Journal of Medicine in 1993. Findings from one of these studies are presented in Figure 9.1, where it can be seen that even short-term use of vitamin E supplements was associated with reduced CHD risk, which persisted after adjustment for confounding factors. demonstrates that nearly half of U.S. adults are taking either vitamin E supplements or multivitamin/multimineral supplements that generally contain vitamin E (Radimer et al., 2004). presents data from three available time points, where there appears to have been a particular increase in vitamin E use following 1993 (Millen, Dodd, & Subar, 2004), possibly consequent upon the publication of the two observational studies already mentioned, which have received nearly 3,000 citations between them since publication. The apparently strong observational evidence with respect to vitamin E and reduced CHD risk, which may have influenced the very high current use of vitamin E supplements in developed countries, was unfortunately not realized in RCTs, in which no benefit from vitamin E supplementation use is seen.

Keywords:   Associative selection bias, Canalization, Developmental stability, Exposure propensity, Genetic variation, Heart Protection Study, Intermediate phenotypes, Linkage disequilibrium, Phenocopy

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